The assembly of the head of bacteriophage T4 is being studied as a model system for discovering the mechanisms by which multimolecular structures are synthesized in cells. We are determining the role of the minor head components, and the scaffolding core of the prehead in determining the form of the mature head. We use immunoelectronmicroscopy to localize specific antigens in head-related structures, and optical diffraction and filtration of electron micrographs to analyze the structure of periodically repeating head-related assemblies. We have purified the T4 coded proteinase and are studying the mechanisms by which its zymogen is activated, and its intracellular acivity is regulated. Fab fragment labelling coupled with image processing of electron micrographs is being used to determine conformational changes which occur in the principal prehead shell protein during its cleavage and the expansion which leads to the formation of the mature capsid. Immunoreplicate electrophoresis is used to assay for nanogram levels of phage related antigen in crude lysates.